875 ISSN 2041-5990 10.4155/TDE.12.55 © 2012 Future Science Ltd Therapeutic Delivery (2012) 3(7), 875–887 Review The development of drug-loaded nanocarriers to vehiculate active principles to a target site is an emerging topic in the field of nanoscience. Recently, several systems have been developed for the treatment of various neurological dis- orders. The main advantages of using nanocar- riers are: protection of the active principle from the biological environment; enhanced transport through biological barriers; and targeted trans- port to specific cells or tissues, with the final goal to improve efficacy and safety of the pharmaco- logical treatment. All these characteristics are related to the extreme versatility of nanocarriers, which can be functionalized and designed to be responsive to external stimuli [1,2] . Nanocarriers provide a promising approach for the delivery of various agents, including drugs [3] , proteins [4,5] and nucleic acids [6] . Several nanoparticu- late systems have been designed for applications in cancer therapy [7–11] and in other biomedi- cal fields [12–18] , such as the treatment of neu- rodegenerative diseases [19–22] . On the basis of the desired characteristics, nanocarriers can be prepared using metallic, inorganic or organic (e.g., polymeric) materials. Polymeric particles show some advantages with respect to other nanocarriers, due to the possibility to specifi- cally tailor polymeric macromolecules and fine- tune their chemical properties, thus controlling biocompatibility and delivery kinetics. In addi- tion, polymers can be chemically modified to facilitate conjugation with functional groups for targeted delivery of the nanocarrier, for example, through biological barriers. Numerous papers in the literature report the encouraging use of poly- meric nanoparticles (NPs) for targeted transport to the CNS [23–25] . The CNS is protected by the presence of the blood–brain barrier (BBB) [26] , a physiological barrier preventing potentially harmful substances from entering the brain from the blood. Among these substances, the BBB can stop drugs and therapeutic agents admin- istered via the systemic route [27] . The present paper reviews the use of polymeric nanocarri- ers administered systemic routes for the deliv- ery of therapeutic agents for the treatment of neurological pathologies. Polymeric nanostructures In recent years, the interest in polymeric nanoparticulate systems for the targeted drug delivery to the brain has increased [28] . NPs can be used as carriers of therapeutic agents to improve bioavailability and biodistribution, cell and tissue uptake, delivery kinetics and pharmacological activity. In addition, polymeric materials are simple to manufacture in a wide range of nanostructures that differ in shape, size and molecular architecture and arrange- ment. Morphological and structural properties of polymeric nanostructures can be accurately controlled by fine tuning process parameters, thus improving the performances of the carriers. Among the large variety of structures that can be obtained, it is possible to identify some main classes, such as NPs, micelles and dendrimers. NPs are generally defined as structures with dimensions between 1 and 100 nm, forming Polymeric nanocarriers for controlled and enhanced delivery of therapeutic agents to the CNS Polymeric nanocarriers are versatile structures that can be engineered to obtain high drug loading, good delivery yields and tunable release kinetics. Moreover, the particle surface can be modiied for selective targeting of organs or tissues. In particular, polymeric nanocarriers can be conjugated with functional groups promoting translocation through the blood–brain barrier, thus providing a promising system to deliver therapeutic agents and/or diagnostic probes to the brain. Here we review recent literature on the preparation and characterization of polymeric nanoparticles as potential agents for drug delivery to the CNS, with an emphasis on materials chemistry and functionalization strategies for improved selectivity and delivery. Finally, we underline the immunotoxicological aspects of this class of nanostructured materials in view of potential clinical applications. Mariacristina Gagliardi*, Giuseppe Bardi & Angelo Bifone Center for Nanotechnology Innovation @NEST, Istituto Italiano di Tecnologia, Piazza San Silvestro 12, 56127, Pisa, Italy *Author for correspondence: Tel.: +39 050 509119 E-mail: mariacristina.gagliardi@iit.it